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Previous research has demonstrated a robust association between osteoarthritis (OA) and psoriasis. Notably, a significant proportion of psoriasis patients exhibit symptoms of arthritis, particularly psoriatic arthritis. However, a definitive causal relationship between psoriasis, psoriatic arthritis and OA remains to be established. This study aimed to elucidate the causal relationship between psoriasis, psoriatic arthritis, and osteoarthritis using a 2-sample Mendelian randomization approach. The causal relationship between psoriasis, psoriatic arthritis and OA was rigorously investigated using a 2-sample Mendelian Randomization (MR) approach. Instrumental variables pertinent to psoriasis, psoriatic arthritis and 4 distinct types of OA (knee osteoarthritis (KOA), hand osteoarthritis (HOA), total knee replacement (TKR), and total hip replacement (THR)) were sourced from extensive, published genome-wide association studies (GWAS). To estimate the causal effects, methodologies such as inverse variance weighting (IVW), MR-Egger, and weighted median estimation (WM) were employed. Mendelian Randomization analysis suggested a potential causal effect of psoriasis on osteoarthritis (OA). For hand OA (HOA), the P value was .381 (ORâ =â 0.28); for knee OA (KOA), the P value was .725 (ORâ =â 1.46); for TKR, the P value was .488 (ORâ =â 0.274); and for THR, the P value was .454 (ORâ =â 0.216). Furthermore, we explored the causality of psoriatic arthritis on OA. For HOA, the P value was .478 (ORâ =â 0.0095); for KOA, the P value was .835 (ORâ =â 0.345); for THR, the P value was .807 (ORâ =â 0.120); and for TKR, the P value was .860 (ORâ =â 0.190). Our findings indicate that there is no evidence of a causal connection between psoriasis or psoriatic arthritis and OA, suggesting that while psoriasis may contribute to arthritis, it does not influence OA development.
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Artritis Psoriásica , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Osteoartritis , Psoriasis , Humanos , Psoriasis/genética , Psoriasis/complicaciones , Psoriasis/epidemiología , Osteoartritis/genética , Osteoartritis/epidemiología , Artritis Psoriásica/genética , Artritis Psoriásica/complicaciones , Osteoartritis de la Rodilla/genética , Osteoartritis de la Rodilla/epidemiología , Causalidad , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de RodillaRESUMEN
Lightweight ablative thermal protection materials (TPMs), which can resist long-term ablation in an oxidizing atmosphere, are urgently required for aerospace vehicles. Herein, carbon fabric/phenol-formaldehyde resin/siloxane aerogels (CF/PFA/SiA) nanocomposite with interpenetrating network multiscale structure was developed via simple and efficient sol-gel followed by atmospheric pressure drying. The ternary networks structurally interpenetrating in macro-, micron-, and the nanoscales, chemically cross-linking at the molecular scale, and silica layer generated by in situ heating synergistically bring about low density (â¼0.3 g cm-3), enhanced mechanical properties, thermal stability, and oxidation resistance, and a low thermal conductivity of 81 mW m-1 K-1. More intriguingly, good thermal protection with near-zero surface recession at 1300 °C for 300 s and remarkable thermal insulation with a back-side temperature below 60 °C at 20 mm thickness. The interpenetrating network strategy can be extended to other porous components with excellent high-temperature properties, such as ZrO2 and SiC, which will facilitate the improvement of lightweight ablative TPMs. Moreover, it may open a new avenue for fabricating multifunctional binary, ternary, and even multiple interpenetrating network materials.
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Background: Acute liver injury (ALI), which is a type of inflammation-mediated hepatocellular injury, is a clinical syndrome that results from hepatocellular apoptosis and hemorrhagic necrosis. Apoptosis stimulating protein of p53-2 (ASPP2) is a proapoptotic member of the p53 binding protein family. However, the role of ASPP2 in the pathogenesis of ALI and its regulatory mechanisms remain unclear. Methods: The expression of ASPP2 were compared between liver biopsies derived from patients with CHB, patients with ALI, and normal controls. Acute liver injury was modelled in mice by administration of D-GalN/LPS. Liver injury was demonstrated by serum transaminases and histological assessment of liver sections. ASPP2-knockdown mice (ASPP2+/-) were used to determine its role in acute liver injury. Mouse bone marrow macrophages (BMMs) were isolated from wildtype and ASPP2+/- mice and stimulated with LPS, and the supernatant was collected to incubate with the primary hepatocytes. Quantitative real-time PCR and western blot were used to analyze the expression level of target. Results: The expression of ASPP2 was significantly upregulated in the liver tissue of ALI patients and acute liver injury mice. ASPP2+/- mice significantly relieved liver injury through reducing liver inflammation and decreasing hepatocyte apoptosis. Moreover, the conditioned medium (CM) of ASPP2+/- bone marrow-derived macrophages (BMMs) protected hepatocytes against apoptosis. Mechanistically, we revealed that ASPP2 deficiency in BMMs specifically upregulated IL-6 through autophagy activation, which decreased the level of TNF-α to reduce hepatocytes apoptosis. Furthermore, up-regulation of ASPP2 sensitizes hepatocytes to TNF-α-induced apoptosis. Conclusion: Our novel findings show the critical role of ASPP2 in inflammatory immunoregulatory mechanism of ALI and provide a rationale to target ASPP2 as a refined therapeutic strategy to ameliorate acute liver injury.
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Proteínas Reguladoras de la Apoptosis , Apoptosis , Animales , Humanos , Ratones , Masculino , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/genética , Ratones Noqueados , Hígado/patología , Hígado/metabolismo , Hígado/inmunología , Hepatocitos/metabolismo , Hepatocitos/patología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Inflamación/inmunología , Inflamación/metabolismo , Femenino , Lipopolisacáridos , Persona de Mediana Edad , Macrófagos/inmunología , Macrófagos/metabolismo , Adulto , Proteínas Supresoras de TumorRESUMEN
Long non-coding RNAs (lncRNAs) are RNA sequences exceeding 200 nucleotides in length that lack protein-coding capacity and participate in diverse biological processes in the human body, particularly exerting a pivotal role in disease surveillance, diagnosis, and progression. Taurine upregulated gene 1 (TUG1) is a versatile lncRNA, and recent studies have revealed that the aberrant expression or function of TUG1 is intricately linked to the pathogenesis of liver diseases. Consequently, we have summarized the current understanding of the mechanism of TUG1 in liver diseases such as liver fibrosis, fatty liver, cirrhosis, liver injury, hepatitis, and liver cancer. Moreover, mounting evidence suggests that interventions targeting TUG1 or its downstream pathways may hold therapeutic promise for liver diseases. This review elucidates the characteristics, mechanisms, and targets of TUG1 in liver diseases, offering a theoretical basis for the prevention, diagnosis, treatment, and prognostic biomarkers of liver diseases.
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Hepatopatías , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Hepatopatías/genética , Hepatopatías/diagnóstico , Hepatopatías/metabolismoRESUMEN
As one of the most serious complications of sepsis, sepsis-associated encephalopathy has not been effectively treated or prevented. Exosomes, as a new therapeutic method, play a protective role in neurodegenerative diseases, stroke and traumatic brain injury in recent years. The purpose of this study was to investigate the role of exosomes in glutamate (Glu)-induced neuronal injury, and to explore its mechanism, providing new ideas for the treatment of sepsis-associated encephalopathy. The neuron damage model induced by Glu was established, and its metabolomics was analyzed and identified. BV2 cells were induced to differentiate into M1 and M2 subtypes. After the exosomes from both M1-BV2 cells and M2-BV2 cells were collected, exosome morphological identification was performed by transmission electron microscopy and exosome-specific markers were also detected. These exosomes were then cocultured with HT22 cells. CCK-8 method and LDH kit were used to detect cell viability and toxicity. Cell apoptosis, mitochondrial membrane potential and ROS content were respectively detected by flow cytometry, JC-1 assay and DCFH-DA assay. MiR-124-3p expression level was detected by qRT-PCR and Western blot. Bioinformatics analysis and luciferase reporter assay predicted and verified the relationship between miR-124-3p and ROCK1 or ROCK2. Through metabolomics, 81 different metabolites were found, including fructose, GABA, 2, 4-diaminobutyric acid, etc. The enrichment analysis of differential metabolites showed that they were mainly enriched in glutathione metabolism, glycine and serine metabolism, and urea cycle. M2 microglia-derived exosomes could reduce the apoptosis, decrease the accumulation of ROS, restore the mitochondrial membrane potential and the anti-oxidative stress ability in HT22 cells induced by Glu. It was also found that the protective effect of miR-124-3p mimic on neurons was comparable to that of M2-EXOs. Additionally, M2-EXOs might carry miR-124-3p to target ROCK1 and ROCK2 in neurons, affecting ROCK/PTEN/AKT/mTOR signaling pathway, and then reducing Glu-induced neuronal apoptosis. M2 microglia-derived exosomes may protect HT22 cells against Glu-induced injury by transferring miR-124-3p into HT22 cells, with ROCK being a target gene for miR-124-3p.
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BACKGROUND/PURPOSE: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is capable of causing serious community and hospital-acquired infections. However, currently, the identification of CRKP is complex and inefficient. Hence, this study aimed to develop methods for the early and effective identification of CRKP to allow reasonable antimicrobial therapy in a timely manner. METHODS: K. pneumoniae (KP)-, K. pneumoniae carbapenemase (KPC)- and New Delhi metallo-ß-lactamase (NDM)- specific CRISPR RNAs (crRNAs), polymerase chain reaction (PCR) primers and recombinase-aided amplification (RAA) primers were designed and screened in conserved sequence regions. We established fluorescence and lateral flow strip assays based on CRISPR/Cas13a combined with PCR and RAA, respectively, to assist in the detection of CRKP. Sixty-one clinical strains (including 51 CRKP strains and 10 carbapenem-sensitive strains) were collected for clinical validation. RESULTS: Using the PCR-CRISPR assay, the limit of detection (LOD) for KP and the blaKPC and blaNDM genes reached 1 copy/µL with the fluorescence signal readout. Using the RAA-CRISPR assay, the LOD could reach 101 copies/µL with both the fluorescence signal readout and the lateral flow strip readout. Additionally, the positivity rates of CRKP-positive samples detected by the PCR/RAA-CRISPR fluorescence and RAA-CRISPR lateral flow strip methods was 92.16% (47/51). The sensitivity and specificity reached 100% for KP and blaKPC and blaNDM gene detection. For detection in a simulated environmental sample, 1 CFU/cm2 KP could be detected. CONCLUSION: We established PCR/RAA-CRISPR assays for the detection of blaKPC and blaNDM carbapenemase genes, as well as KP, to facilitate the detection of CRKP.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/metabolismo , Sistemas CRISPR-Cas , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Infecciones por Klebsiella/tratamiento farmacológicoRESUMEN
Salinity is a severe abiotic stress that limits plant survival, growth, and development. 14-3-3 proteins are phosphopeptide-binding proteins that are involved in numerous signaling pathways, such as metabolism, development, and stress responses. However, their roles in salt tolerance are unclear in woody plants. Here, we characterized an apple (Malus domestica) 14-3-3 gene, GENERAL REGULATORY FACTOR 8 (MdGRF8), the product of which promotes salinity tolerance. MdGRF8 overexpression improved salt tolerance in apple plants, whereas MdGRF8-RNA interference (RNAi) weakened it. Yeast 2-hybrid, bimolecular fluorescence complementation, pull-down, and coimmunoprecipitation assays revealed that MdGRF8 interacts with the transcription factor MdWRKY18. As with MdGRF8, overexpressing MdWRKY18 enhanced salt tolerance in apple plants, whereas silencing MdWRKY18 had the opposite effect. We also determined that MdWRKY18 binds to the promoters of the salt-related genes SALT OVERLY SENSITIVE 2 (MdSOS2) and MdSOS3. Moreover, we showed that the 14-3-3 protein MdGRF8 binds to the phosphorylated form of MdWRKY18, enhancing its stability and transcriptional activation activity. Our findings reveal a regulatory mechanism by the MdGRF8-MdWRKY18 module for promoting the salinity stress response in apple.
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Malus , Tolerancia a la Sal , Tolerancia a la Sal/genética , Malus/metabolismo , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estrés Fisiológico/genéticaRESUMEN
Background and Aims Coinfection of hepatitis delta virus (HDV) with hepatitis B virus (HBV) causes the most severe form of viral hepatitis, and the global prevalence of HDV infection is underestimated. Although serological testing of anti-HDV antibodies is widely used in the diagnosis of HDV, its diagnostic efficacy remains unclear. This study aimed to evaluate the diagnostic efficacy of HDV serological tests, the results of which may assist in the diagnosis of HDV. Methods Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. The PubMed, Web of Science and Cochrane Library databases were searched from the beginning to 31 May 2023. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. STATA SE was used for the meta-analysis of the sensitivity, specificity, positive likelihood ratio and negative likelihood ratio. Results Among a total of 1376 initially identified studies, only 12 articles met the final inclusion criteria. The pooled sensitivity and specificity were 1.00 (95% CI: 0.00-1.00) and 0.71 (95% CI: 0.50-0.78) for HDV total antibodies, 0.96 (95% CI: 0.83-0.99) and 0.98 (95% CI: 0.82-1.00) for anti-HDV IgM and 0.95 (95% CI: 0.86-0.98) and 0.96 (95% CI: 0.67-1.00) for anti-HDV IgG. The pooled sensitivity and specificity for HDV serological tests were 0.99 (95% CI: 0.96-1.00) and 0.90 (95% CI: 0.79-0.96). Conclusions This meta-analysis suggests that serological tests have high diagnostic performance in detecting antibodies against HDV, especially in HDV IgM and IgG. However, this conclusion is based on studies of a limited number and quality, and the development of new diagnostic tools with higher precision and reliability is still necessary.
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Hepatitis B , Humanos , Virus de la Hepatitis Delta , Reproducibilidad de los Resultados , Anticuerpos Antihepatitis , Inmunoglobulina M , Inmunoglobulina GRESUMEN
BACKGROUND & AIMS: Hepatitis delta virus (HDV) infection accelerates the progression of chronic hepatitis B virus (HBV) infection, posing a large economic and health burden to patients. At present, there remains a lack of accurate and portable detection methods for HDV RNA. Here, we aim to establish a convenient, rapid, highly sensitive and specific method to detect HDV RNA using CRISPR-Cas13a technology. METHODS: We established fluorescence (F) and lateral flow strip (L) assays based on CRISPR-Cas13a combined with RT-PCR and RT-RAA for HDV RNA detection, respectively. we conducted a cohort study of 144 patients with HDV-IgG positive to evaluate the CRISPR-Cas13a diagnostic performance for identifying HDV in clinical samples, compared to RT-qPCR and RT-ddPCR. RESULTS: For synthetic HDV RNA plasmids, the sensitivity of RT-PCR-CRISPR-based fluorescence assays was 1 copy/µL, higher than that of RT-qPCR (10 copies/µL) and RT-ddPCR (10 copies/µL); for HDV RNA-positive samples, the sensitivity of RT-RAA-CRISPR-based fluorescence and lateral flow strip assays was 10 copies/µL, as low as that of RT-qPCR and RT-ddPCR, and the assay took only approximately 85 min. Additionally, the positivity rates of anti-HDV IgG-positive samples detected by the RT-qPCR, RT-ddPCR, RT-PCR-CRISPR fluorescence and RT-RAA-CRISPR lateral flow strip methods were 66.7% (96/144), 76.4% (110/144), 81.9% (118/144), and 72.2% (104/144), respectively. CONCLUSIONS: We developed a highly sensitive and specific, as well as a portable and easy CRISPR-based assay for the detection of HDV RNA, which could be a prospective measure for monitoring the development of HDV infection and evaluating the therapeutic effect.
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Hepatitis B Crónica , Virus de la Hepatitis Delta , Humanos , Virus de la Hepatitis Delta/genética , Estudios de Cohortes , Estudios Prospectivos , ARN Viral/genética , Inmunoglobulina G , Sensibilidad y EspecificidadRESUMEN
Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.
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Exosomas , Vesículas Extracelulares , Sepsis , Choque Séptico , Humanos , Choque Séptico/terapia , Exosomas/metabolismo , Sepsis/diagnóstico , Sepsis/terapia , Vesículas Extracelulares/metabolismo , ARN/metabolismoRESUMEN
Background and Aims: Hepatitis delta virus (HDV) is a defective virus and causes severe liver disease. Several HDV RNA assays have been developed, however the diagnostic efficacy remains unclear.This systematic review and meta-analysis aims to evaluate the diagnostic accuracy of HDV RNA assays to aid in the diagnosis of active hepatitis D. Methods: The PubMed, Embase, and Cochrane Library databases were systematically searched from the beginning to June 31, 2022. Information on the characteristics of the literature and data on sensitivity, specificity, and area under curve (AUC) of the receiver operating characteristic (ROC) were extracted. Stata 14.0 was used for meta-analysis of the combined sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Results: A total of 10 studies were included in the meta-analysis. The summary sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of HDV RNA assays for HDV diagnosis were 0.92 (95% CI: 0.87-0.95), 0.90 (95% CI: 0.86-0.93), 7.74 (95% CI: 5.31-11.29), 0.10 (95% CI: 0.06-0.18) and 99.90 (95% CI: 47.08-211.99), respectively. The AUC of the pooled ROC curve was 0.95 (95% CI: 0.92-0.96). Conclusions: The results show that HDV RNA assays had high diagnostic performance. However, that is limited by the number and quality of studies. Standard protocols for the development of assays by manufacturers and larger studies on the use of the assays are needed.
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Objective: A vicious cycle between circadian disruption and escalating immune responses has been described in diverse inflammatory disease. The current study aimed to explore the role of circadian clock disruption in autoimmune thyroiditis (AIT). Methods: Thirty AIT patients and 30 controls were enrolled and biopsied for thyroid tissues. Alterations of core clock genes expression in AIT thyroid tissues, and its association with serum and tissue inflammatory biomarkers were assessed. For animal studies, C57BL/6J mice administered with porcine thyroglobulin or PBS (as control) combined with adjuvants were sacrificed at four time points to investigate the circadian characteristic of experimental autoimmune thyroiditis (EAT). Light shift (LS) conditions were used to explore the influence of external circadian disturbance on EAT. Results: The expression of clock genes BMAL1 and PER2 was significantly reduced in thyroid tissues from AIT patients and was negatively correlated to levels of thyroid peroxidase antibodies. In mouse models, diurnal fluctuations of proinflammatory cytokines were demonstrated, and further exposing mice to LS led to overproduction of TNF-α, IFN-γ, and anti-thyroglobulin antibodies. Circadian analysis revealed significant oscillations of Bmal1, Clock, Per2, Cry1, Ror, and Rev-erb, which was broadly disturbed in EAT, LS, and EAT + LS groups. Conclusions: This study demonstrates that expression pattern of clock genes was disrupted in AIT thyroid, and chronic circadian disruption may aggravate the inflammatory responses in AIT. Whether maintaining a regular circadian rhythm can alleviate autoimmune thyroid diseases warrants further research.
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Relojes Circadianos , Enfermedad de Hashimoto , Tiroiditis Autoinmune , Ratones , Animales , Porcinos , Tiroiditis Autoinmune/genética , Relojes Circadianos/genética , Factores de Transcripción ARNTL/genética , Ratones Endogámicos C57BLRESUMEN
A high-purity germanium (HPGe) gamma-ray spectrometer and an Alpha-GUARD radon monitor are the activity and activity concentration transfer standards of 222Rn, respectively. The gaseous 222Rn standard source traceable to the NIM's absolute standardization apparatus of 222Rn was developed for calibrating these transfer standards. The calibration results of HPGe detector at three different distances show that the uncertainties of experimental efficiency are less than 0.77% (k = 1). Meanwhile, the Monte Carlo (MC) simulation was carried out at wider distances range for the HPGe calibration as well, and the deviation at same three distances between experiments and simulations results is within ±3.0%. The advantage of calibration using MC simulation and the possible reasons for the deviation were discussed in detail in this article. In addition, a reference activity concentration environment based on the gaseous 222Rn standard source was also developed to calibrate the radon monitor, and the typical uncertainty for calibration factor of Alpha-GUARD radon monitor could be reduced to 1.9% (k = 1).
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BACKGROUND: Accurately predicting the risk of atherosclerotic cardiovascular disease (ASCVD) is crucial for implementing individualized prevention strategies and improving patient outcomes. Our objective is to develop machine learning (ML)-based models for predicting ASCVD risk in a prospective Chinese population and compare their performance with conventional regression models. METHODS: A hybrid dataset consisting of 551 features was used, including 98 demographic, behavioral, and psychological features, 444 Electrocardiograph (ECG) features, and 9 Echocardiography (Echo) features. Seven machine learning (ML)-based models were trained, validated, and tested after selecting the 30 most informative features. We compared the discrimination, calibration, net benefit, and net reclassification improvement (NRI) of the ML models with those of conventional ASCVD risk calculators, such as the Pooled Cohort Equations (PCE) and Prediction for ASCVD Risk in China (China-PAR). RESULTS: The study included 9,609 participants (mean age 53.4 ± 10.4 years, 53.7% female), and during a median follow-up of 4.7 years, 431 (4.5%) participants developed ASCVD. In the testing set, the final ML-based ANN model outperformed PCE, China-PAR, recalibrated PCE, and recalibrated China-PAR in predicting ASCVD. This was demonstrated by the model's higher area under the curve (AUC) of 0.800, compared to 0.777, 0.780, 0.779, and 0.779 for the other models, respectively. Additionally, the model had a lower Hosmer-Lemeshow χ2 of 9.1, compared to 37.3, 67.6, 126.6, and 18.6 for the other models. The net benefit at a threshold of 5% was also higher for the ML-based ANN model at 0.017, compared to 0.016, 0.013, 0.017, and 0.016 for the other models, respectively. Furthermore, the NRI was 0.089 for the ML-based ANN model, while it was 0.355, 0.098, and 0.088 for PCE, China-PAR, and recalibrated PCE, respectively. CONCLUSIONS: Compared to conventional regression ASCVD risk calculators, such as PCE and China-PAR, the ANN prediction model may help optimize identification of individuals at heightened cardiovascular risk by flexibly incorporating a wider range of potential predictors. The findings may help guide clinical decision-making and ultimately contribute to ASCVD prevention and management.
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Aterosclerosis , Enfermedades Cardiovasculares , Aprendizaje Automático , Modelos Cardiovasculares , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Pueblos del Este de Asia , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , ChinaRESUMEN
The accuracy of activity determination for activated nuclide 56Mn is the key to the manganese bath method applying to the characterization of radionuclide neutron source. As an alternative to the 4π(C)-γ method, TDCR-Cerenkov method could also be applied to the measurement of 56Mn in the manganese bath device, if the existing calculation model is extended. There are two difficulties when the existing TDCR-Cerenkov method is applied to the activity determination of 56Mn. One is that the efficiency computation of gamma transitions, and the other is the interference contributed by Cerenkov photons emitted in the photomultiplier windows induced by Compton scattering. In this study, the above two difficulties are solved by extending the calculation model. For efficiency computation, the decay scheme of 56Mn is taken into account in the calculation of efficiency. Among them, the efficiency of gamma transition is calculated from the simulated secondary electronic spectra. In addition, Cerenkov photons emitted in photomultiplier windows are corrected by additional light proof experiment and improved calculation model. The results derived from this extended method are in good agreement with other standardization technique.
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BACKGROUND: Hypertension can lead to podocyte damage and subsequent apoptosis, eventually resulting in glomerulosclerosis. Although alleviating podocyte apoptosis has clinical significance for the treatment of hypertensive nephropathy, an effective therapeutic target has not yet been identified. The function of septin4, a proapoptotic protein and an important marker of organ damage, is regulated by post-translational modification. However, the exact role of septin4 in regulating podocyte apoptosis and its connection to hypertensive renal damage remains unclear. METHODS: We investigated the function and mechanism of septin4 in hypertensive nephropathy to discover a theoretical basis for targeted treatment. Mouse models including Rosa 26 (Gt(ROSA)26Sor)-SIRT2 (silent mating type information regulation 2 homolog-2)-Flag-TG (transgenic) (SIRT2-TG) mice SIRT2-knockout, and septin4-K174Q mutant mice, combined with proteomic and acetyl proteomics analysis, followed by multiple molecular biological methodologies, were used to demonstrate mechanisms of SIRT2-mediated deacetylation of septin4-K174 in hypertensive nephropathy. RESULTS: Using transgenic septin4-K174Q mutant mice treated with the antioxidant Tempol, we found that hyperacetylation of the K174 site of septin4 exacerbates Ang II (angiotensin II)- induced hypertensive renal injury resulting from oxidative stress. Proteomics and Western blotting assays indicated that septin4-K174Q activates the cleaved-PARP1 (poly [ADP-ribose] polymerase family, member 1)-cleaved-caspase3 pathway. In septin4-knockdown human renal podocytes, septin4-K174R, which mimics deacetylation at K174, rescues podocyte apoptosis induced by Ang II. Immunoprecipitation and mass spectrometry analyses identified SIRT2 as a deacetylase that interacts with the septin4 GTPase domain and deacetylates septin4-K174. In Sirt2-deficient mice and SIRT2-knockdown renal podocytes, septin4-K174 remains hyperacetylated and exacerbates hypertensive renal injury. By contrast, in Rosa26-Sirt2-Flag (SIRT2-TG) mice and SIRT2-knockdown renal podocytes reexpressing wild-type SIRT2, septin4-K174 is hypoacetylated and mitigates hypertensive renal injury. CONCLUSIONS: Septin4, when activated through acetylation of K174 (K174Q), promotes hypertensive renal injury. Septin4-K174R, which mimics deacetylation by SIRT2, inhibits the cleaved-PARP1-cleaved-caspase3 pathway. Septin4-K174R acts as a renal protective factor, mitigating Ang II-induced hypertensive renal injury. These findings indicate that septin4-K174 is a potential therapeutic target for the treatment of hypertensive renal injury.
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Hipertensión Renal , Hipertensión , Animales , Humanos , Ratones , Apoptosis , Hipertensión Renal/genética , Riñón/metabolismo , Ratones Transgénicos , Proteómica , Sirtuina 2/genética , Sirtuina 2/metabolismoRESUMEN
BACKGROUND & AIMS: The WHO declared to eliminate hepatitis B virus (HBV) by 2030. However, an increasing number of patients are presenting with low-level viremia (LLV) with the widespread use of antiviral medications. The diagnostic efficiency and coverage area of HBV infection are low. Hence, this study intended to drive the HBV infection detection to effectively adaptable for any small to medium-sized laboratory or field survey. METHODS: We established, optimized, and evaluated a colloidal gold test strip for detection of HBV DNA based on CRISPR/Cas13a combined with recombinase-aided amplification (RAA) technology. Furthermore, 180 HBV-infected patients (including patients with different viral loads, LLV patients and dynamic plasma samples of patients on antiviral therapy) were enrolled for clinical validation. RESULTS: The strip detection of HBV DNA was established based on RAA-CRISPR-Cas13a technology with a sensitivity of 101 copies/µL and a specificity of 100%. HBV DNA gradient concentration plasmids and clinical samples were effectively identified by this approach. The positive coincidence rate for LLV patients was 87%, while the negative coincidence rate was 100%. The positive coincidence rate reached 100% in LLV patients (viral loading >100 IU/mL). The sensitivity, specificity, positive predictive agreement (PPA) and negative predictive agreement (NPA) values of dynamic plasma detection in patients on antiviral therapy were 100%, 92.15%, 93.75%, and 100%, respectively. CONCLUSIONS: We develop rapid and portable RAA-CRISPR/Cas13a-based strip of HBV DNA detection for LLV patients. This study provides a visual and faster alternative to current PCR-based diagnosis for HBV infection.
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ADN Viral , Hepatitis B , Humanos , ADN Viral/genética , Viremia/diagnóstico , Viremia/tratamiento farmacológico , Viremia/genética , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Sensibilidad y Especificidad , Hepatitis B/genética , Virus de la Hepatitis B/genética , Antivirales/uso terapéuticoRESUMEN
Realizing strong laser-matter interaction in a heterostructure consisting of two-dimensional transition metal dichalcogenides (TMDCs) and an optical nanocavity is a potential strategy for novel photonic devices. In this paper, two core-Ω shell nanostructures, Si@WS2 core-Ω shell nanostructure on glass/Si substrates, are briefly introduced. A strong laser-matter interaction occurred in the Si@WS2 core-Ω shell nanostructure when it was excited by femtosecond (fs) laser in the near-infrared-1 region (NIR-1, 650 nm-950 nm), resulting in a resonance coupling between the electric dipole resonance (EDR) of the Si nanosphere (NS) and the exciton resonance of the WS2 nanomembrane (NMB). The generation of resonance coupling regulates the resonant mode of the nanostructure to realize the multi-dimensional nonlinear optical response, which can be utilized in the fields of biological imaging and nanoscale light source.
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BACKGROUND: Hepatitis delta virus (HDV) is a satellite RNA virus that relies on hepatitis B virus (HBV) for transmission. HIV/HBV/HDV coinfection or triple infection is common and has a worse prognosis than monoinfection. OBJECTIVE: We aimed to reveal the epidemiological characteristics of HIV/HBV/HDV triple infection in the global population. METHODS: A systematic literature search in PubMed, Embase, and the Cochrane Library was performed for studies of the prevalence of HIV/HBV/HDV triple infection published from January 1, 1990, to May 31, 2021. The Der Simonian-Laird random effects model was used to calculate the pooled prevalence. RESULTS: We included 14 studies with 11,852 participants. The pooled triple infection rate in the global population was 7.4% (877/11,852; 95% CI 0.73%-29.59%). The results of the subgroup analysis showed that the prevalence of triple infection was significantly higher in the Asian population (214/986, 21.4%; 95% CI 7.1%-35.8%), in men (212/5579, 3.8%; 95% CI 2.5%-5.2%), and in men who have sex with men (216/2734, 7.9%; 95% CI 4.3%-11.4%). In addition, compared with people living with HIV, the HIV/HBV/HDV triple infection rate was higher in people with hepatitis B. CONCLUSIONS: This meta-analysis suggests that the prevalence of HIV/HBV/HDV triple infection in the global population is underestimated, and we should focus more effort on the prevention and control of HIV/HBV/HDV triple infection. TRIAL REGISTRATION: PROSPERO CRD42021273949; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=273949.
Asunto(s)
Virus de la Hepatitis Delta , Minorías Sexuales y de Género , Masculino , Humanos , Virus de la Hepatitis B , Prevalencia , Homosexualidad MasculinaRESUMEN
The electrode, as one of the most critical components in a proton exchange membrane water electrolysis (PEMWE) cell for hydrogen production, has a significant impact on cell performance. Electrodes that are fabricated via various techniques may exhibit different morphologies or properties, which might change the kinetics and resistances of the PEMWE. In this study, we have successfully fabricated several electrodes by different techniques, and the effects of electrode coating methods (ultrasonic spray, blade coating, and rod coating), hot press, and decal transfer processes are comprehensively investigated. The performance differences between various electrodes are due to kinetic or high frequency resistance changes, while the influences are not significant, with the biggest deviation of about 26 mV at 2.0 A cm-2. In addition, the effects of catalyst ink compositions, including ionomer to catalyst ratio (0.1 to 0.3), water to alcohol ratio (1:1 to 3:1), and catalyst weight percentage (10% to 30%), are also studied, and the electrodes' performance variations are less than 10 mV at 2.0 A cm-2. The results show that the PEMWE electrode has superior compatibility and redundancy, which demonstrates the high flexibility of the electrode and its applicability for large-scale manufacturing.